Sex Hormones and Sex Chromosomes Cause Sex Differences in the Development of Cardiovascular Diseases

Overview

Journal Arterioscler Thromb Vasc Biol

Date 2017 Mar 11

PMID 28279969

Citations 153

Authors

Arthur P Arnold

Lisa A Cassis

Mansoureh Eghbali

Karen Reue

Kathryn Sandberg

Affiliations

Soon will be listed here.

Abstract

This review summarizes recent evidence concerning hormonal and sex chromosome effects in obesity, atherosclerosis, aneurysms, ischemia/reperfusion injury, and hypertension. Cardiovascular diseases occur and progress differently in the 2 sexes, because biological factors differing between the sexes have sex-specific protective and harmful effects. By comparing the 2 sexes directly, and breaking down sex into its component parts, one can discover sex-biasing protective mechanisms that might be targeted in the clinic. Gonadal hormones, especially estrogens and androgens, have long been found to account for some sex differences in cardiovascular diseases, and molecular mechanisms mediating these effects have recently been elucidated. More recently, the inherent sexual inequalities in effects of sex chromosome genes have also been implicated as contributors in animal models of cardiovascular diseases, especially a deleterious effect of the second X chromosome found in females but not in males. Hormonal and sex chromosome mechanisms interact in the sex-specific control of certain diseases, sometimes by opposing the action of the other.

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References

Cauley J, Gutai J, Glynn N, Cottington E, Kuller L . Serum estrone concentrations and coronary artery disease in postmenopausal women. Arterioscler Thromb. 1994; 14(1):14-8. DOI: 10.1161/01.atv.14.1.14. View

MARSH M, Walker V, Curtiss L, Banka C . Protection against atherosclerosis by estrogen is independent of plasma cholesterol levels in LDL receptor-deficient mice. J Lipid Res. 1999; 40(5):893-900. View

Zhang X, Thatcher S, Wu C, Daugherty A, Cassis L . Castration of male mice prevents the progression of established angiotensin II-induced abdominal aortic aneurysms. J Vasc Surg. 2014; 61(3):767-76. PMC: 4099302. DOI: 10.1016/j.jvs.2013.11.004. View

Balaton B, Brown C . Escape Artists of the X Chromosome. Trends Genet. 2016; 32(6):348-359. DOI: 10.1016/j.tig.2016.03.007. View

Peters S, Singhateh Y, MacKay D, Huxley R, Woodward M . Total cholesterol as a risk factor for coronary heart disease and stroke in women compared with men: A systematic review and meta-analysis. Atherosclerosis. 2016; 248:123-31. DOI: 10.1016/j.atherosclerosis.2016.03.016. View

Henriques T, Zhang X, Yiannikouris F, Daugherty A, Cassis L . Androgen increases AT1a receptor expression in abdominal aortas to promote angiotensin II-induced AAAs in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2008; 28(7):1251-6. PMC: 2757112. DOI: 10.1161/ATVBAHA.107.160382. View

Arnold A, Chen X . What does the "four core genotypes" mouse model tell us about sex differences in the brain and other tissues?. Front Neuroendocrinol. 2008; 30(1):1-9. PMC: 3282561. DOI: 10.1016/j.yfrne.2008.11.001. View

Arnal J, Fontaine C, Billon-Gales A, Favre J, Laurell H, Lenfant F . Estrogen receptors and endothelium. Arterioscler Thromb Vasc Biol. 2010; 30(8):1506-12. DOI: 10.1161/ATVBAHA.109.191221. View

Muller M, van den Beld A, Bots M, Grobbee D, Lamberts S, van der Schouw Y . Endogenous sex hormones and progression of carotid atherosclerosis in elderly men. Circulation. 2004; 109(17):2074-9. DOI: 10.1161/01.CIR.0000125854.51637.06. View

10.

Dai-Do D, Espinosa E, Liu G, Rabelink T, Julmy F, Yang Z . 17 beta-estradiol inhibits proliferation and migration of human vascular smooth muscle cells: similar effects in cells from postmenopausal females and in males. Cardiovasc Res. 1996; 32(5):980-5. View

11.

Mikkola T, Turunen P, Avela K, Orpana A, Viinikka L, Ylikorkala O . 17 beta-estradiol stimulates prostacyclin, but not endothelin-1, production in human vascular endothelial cells. J Clin Endocrinol Metab. 1995; 80(6):1832-6. DOI: 10.1210/jcem.80.6.7775630. View

12.

Parker W . Ovarian conservation versus bilateral oophorectomy at the time of hysterectomy for benign disease. Menopause. 2013; 21(2):192-4. DOI: 10.1097/GME.0b013e31829be0a0. View

13.

Stuntz M . Modeling the Burden of Abdominal Aortic Aneurysm in the USA in 2013. Cardiology. 2016; 135(2):127-31. DOI: 10.1159/000446871. View

14.

Caligiuri G, Nicoletti A, Zhou X, Tornberg I, Hansson G . Effects of sex and age on atherosclerosis and autoimmunity in apoE-deficient mice. Atherosclerosis. 1999; 145(2):301-8. DOI: 10.1016/s0021-9150(99)00081-7. View

15.

Becker J, Arnold A, Berkley K, Blaustein J, Eckel L, Hampson E . Strategies and methods for research on sex differences in brain and behavior. Endocrinology. 2004; 146(4):1650-73. DOI: 10.1210/en.2004-1142. View

16.

Eissa M, Mihalopoulos N, Holubkov R, Dai S, Labarthe D . Changes in Fasting Lipids during Puberty. J Pediatr. 2015; 170:199-205. PMC: 4769904. DOI: 10.1016/j.jpeds.2015.11.018. View

17.

Mukherjee T, Dinh H, Chaudhuri G, Nathan L . Testosterone attenuates expression of vascular cell adhesion molecule-1 by conversion to estradiol by aromatase in endothelial cells: implications in atherosclerosis. Proc Natl Acad Sci U S A. 2002; 99(6):4055-60. PMC: 122647. DOI: 10.1073/pnas.052703199. View

18.

Farias J, Tinetti M, Khoury M, Umpierrez G . Low testosterone concentration and atherosclerotic disease markers in male patients with type 2 diabetes. J Clin Endocrinol Metab. 2014; 99(12):4698-703. PMC: 4255118. DOI: 10.1210/jc.2014-2585. View

19.

Shi A, Tao Z, Wei P, Zhao J . Epidemiological aspects of heart diseases. Exp Ther Med. 2016; 12(3):1645-1650. PMC: 4998208. DOI: 10.3892/etm.2016.3541. View

20.

Thatcher S, Zhang X, Woody S, Wang Y, AlSiraj Y, Charnigo R . Exogenous 17-β estradiol administration blunts progression of established angiotensin II-induced abdominal aortic aneurysms in female ovariectomized mice. Biol Sex Differ. 2015; 6:12. PMC: 4485333. DOI: 10.1186/s13293-015-0030-1. View